1. Technical Field of the Invention
The present invention relates to an improved process of producing bepromoline hydrochloride (bepromoline HCl), which is an intermediate used in the production of Amorolfine (AMF) hydrochloride (Amorolfine HCl).
Amorolfine HCl is an active pharmaceutical ingredient (API) formulated into topical anti-mycotic (anti-fungal) compositions.
2. Description of Background and/or Related and/or Prior Art
French Patent No 2,463,767 describes methods of producing Amorolfine HCl and intermediates for such production. In particular, a method for the production of bepromoline base of formula (Ia):
is described, this method involving the step of reacting a compound of the formula (III):
with a compound of the formula (IV):
such that they undergo catalytic hydrogenation to produce bepromoline base. The suggested catalysts are those generally employed for hydrogenation, with specific mention of platinum, palladium, palladiumcarbon or Raney nickel catalysts. No indication is made of the pH of the hydrogenation conditions.
Need continues to exist for improved processes for the production of Amorolfine salts, for example Amorolfine HCl, notably through an improvement in the production of its intermediates, such as bepromoline or a salt of bepromoline as, for example, bepromoline HCl.
As employed herein, the term “bepromoline base” refers to the compound of formula (Ia), the term “bepromoline HCl” refers to the compound of formula (Ib), and the term “Amorolfine HCl” (AMF HCl) refers to the compound of formula (II):
